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1.
Cien Saude Colet ; 29(7): e02912024, 2024 Jul.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38958315

RESUMO

This study examined factors associated with the recurrence of interpersonal violence against children and adolescents in Mato Grosso state, considering cases recorded in the Notifiable Diseases Information System, from 2013 to 2019. Associations between variables were estimated by logistic regression and stratified by age group (children and adolescents). The frequency of recurrent violence against children was 49.0% and, against adolescents, 42.9%. For both, recurrent violence was positively associated with occurrence at home, psychological or emotional violence, aggressors' being more than two, their being relatives and threats being the means of aggression. Neglect or abandonment and male or both-sex aggressors were positively associated with recurrent violence against children. Against adolescents, poor education, sexual violence and intimate-partner aggressors were positively associated with recurrent violence, while other aggressors and firearms or physical force were negatively associated. The findings offer significant contributions to knowledge of factors associated with recurrent violence, which is still little studied in the national and international literature. This is essential in order to inform strategies to reduce the recurrence of violence and protect children and adolescents.


O objetivo do estudo foi analisar os fatores associados à recorrência da violência interpessoal contra crianças e adolescentes em Mato Grosso. Estudo com casos registrados no Sistema Informação de Agravos de Notificação no período de 2013 a 2019. A associação entre as variáveis foi estimada pela regressão logística, estratificada por faixa etária (crianças e adolescentes). A frequência da violência recorrente em crianças foi de 49,0%, e de 42,9% em adolescentes. Para ambos, a violência recorrente associou-se positivamente com ocorrência em residência, violência psicológica/moral, com mais de dois agressores envolvidos, agressores familiares e meio de agressão, ameaça. Para as crianças, negligência/abandono, sexo do agressor masculino ou ambos associaram-se positivamente com a recorrência da violência. Para adolescentes, baixa escolaridade, violência sexual e agressor parceiro íntimo estiveram associados positivamente à recorrência da violência, enquanto outros agressores e arma de fogo ou força corporal associaram-se negativamente. Os resultados trazem contribuições relevantes para o conhecimento dos fatores associados à violência recorrente, ainda pouco estudada na literatura nacional e internacional, sendo fundamental para apoiar estratégias de redução da recorrência da violência e de proteção às crianças e adolescentes.


Assuntos
Recidiva , Humanos , Adolescente , Brasil/epidemiologia , Criança , Masculino , Feminino , Pré-Escolar , Violência/estatística & dados numéricos , Fatores de Risco , Maus-Tratos Infantis/estatística & dados numéricos , Agressão/psicologia , Lactente , Violência por Parceiro Íntimo/estatística & dados numéricos
2.
Healthcare (Basel) ; 12(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38998810

RESUMO

Institutionalized older adults often face complex medication regimens, increasing their risk of adverse drug events due to polypharmacy, overprescribing, medication interactions, or the use of Potentially Inappropriate Medications (PIM). However, data on medication use and associated risks in this population remain scarce. This pilot study aimed to characterize the sociodemographic, clinical and pharmacotherapeutic profiles, and the use of PIM among institutionalized elders residing in Residential Structures for Elderly People (ERPI) in the Faro municipality, located in the Portuguese region of the Algarve. We conducted a cross-sectional study in a non-randomized sample of 96 participants (mean age: 86.6 ± 7.86 years) where trained researchers reviewed medication profiles and identified potentially inappropriate medications using the EU(7)-PIM list. Over 90% of participants exhibited polypharmacy (≥5 medications), with an average of 9.1 ± 4.15 medications per person. About 92% had potential drug interactions, including major and moderate interactions. More than 86% used at least one potentially inappropriate medication, most commonly central nervous system drugs. This pilot study demonstrates that institutionalized older adults may be at high risk of potential medication-related problems. Implementing comprehensive medication review programs and promoting adapted prescribing practices are crucial to optimize medication use and improve the well-being of this vulnerable population.

3.
NAR Genom Bioinform ; 6(3): lqae077, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38962253

RESUMO

The exponential growth of metatranscriptomic studies dedicated to arboviral surveillance in mosquitoes has yielded an unprecedented volume of unclassified sequences referred to as the virome dark matter. Mosquito-associated viruses are classified based on their host range into Mosquito-specific viruses (MSV) or Arboviruses. While MSV replication is restricted to mosquito cells, Arboviruses infect both mosquito vectors and vertebrate hosts. We developed the MosViR pipeline designed to identify complex genomic discriminatory patterns for predicting novel MSV or Arboviruses from viral contigs as short as 500 bp. The pipeline combines the predicted probability score from multiple predictive models, ensuring a robust classification with Area Under ROC (AUC) values exceeding 0.99 for test datasets. To assess the practical utility of MosViR in actual cases, we conducted a comprehensive analysis of 24 published mosquito metatranscriptomic datasets. By mining this metatranscriptomic dark matter, we identified 605 novel mosquito-associated viruses, with eight putative novel Arboviruses exhibiting high probability scores. Our findings highlight the limitations of current homology-based identification methods and emphasize the potentially transformative impact of the MosViR pipeline in advancing the classification of mosquito-associated viruses. MosViR offers a powerful and highly accurate tool for arboviral surveillance and for elucidating the complexities of the mosquito RNA virome.

4.
Saúde debate ; 48(141): e8514, abr.-jun. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1560533

RESUMO

ABSTRACT The goal of this study was to estimate the prevalence of environmental and occupational exposure to pesticides according to sociodemographic factors among cancer patients. It is a cross-sectional study with cancer patients in the state of Mato Grosso. The prevalence of environmental and occupational exposure to pesticides was calculated as to the variables gender, age, macro-region, and education. Pesticide use per agricultural crops in liters was estimated, and a thematic map was constructed following the macro-region of the agricultural economy. Of the 998 patients, most were female (54.9%), aged between 50 and 69 years old (50.1%), had less than eight years of schooling (60.7%), and resided in the South-Central macro-region (55.4%). Regarding environmental and occupational exposure, 53.1% of the patients live or have lived in a municipality with agricultural plantations; 17.4% lived near crops; 43.4% worked in agriculture, livestock, or extractivism; and 22.9% worked or work directly with pesticides. Environmental and occupational exposure was higher in males, in the older age groups, schooling from 0 to 4 years, and in the macro-regions with higher pesticide use. The study concluded that environmental and occupational exposure among cancer patients is associated to sociodemographic characteristics and macro-regions of the agricultural economy.


RESUMO O objetivo deste estudo foi estimar a prevalência de exposição ambiental e ocupacional aos agrotóxicos conforme fatores sociodemográficos entre pacientes com câncer. Trata-se de um estudo observacional de delineamento transversal com pacientes com câncer do estado de Mato Grosso. Foi calculada a prevalência de exposição ambiental e ocupacional aos agrotóxicos conforme as variáveis sexo, faixa etária, região e escolaridade. Foram estimados o uso de agrotóxicos por culturas agrícolas em litros e construído mapa temático segundo a macrorregião de economia agropecuária. Dos 998 pacientes, a maioria era do sexo feminino (54,9%), tinha entre 50 e 69 anos (50,1%), possuía menos de oito anos de escolaridade (60,7%) e residiam na macrorregião Centro-Sul (55,4%). Em relação à exposição ambiental e ocupacional, 53,1% dos pacientes moram ou moraram em município com plantação agrícola, 17,4% residiam próximo à lavoura, 43,4% trabalharam na agricultura, pecuária ou extrativismo e 22,9% trabalharam ou trabalham diretamente com agrotóxicos. A exposição ambiental e ocupacional foi maior no sexo masculino, nas faixas etárias mais elevadas, escolaridade de 0 a 4 anos e nas macrorregiões de maior uso de agrotóxicos. Conclui-se que a exposição ambiental e ocupacional entre pacientes com câncer se associou as características sociodemográficas e macrorregiões de economia agropecuária.

5.
Sci Data ; 11(1): 441, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702328

RESUMO

Photoaging is the premature aging of the skin caused by prolonged exposure to solar radiation. The visual alterations manifest as wrinkles, reduced skin elasticity, uneven skin tone, as well as other signs that surpass the expected outcomes of natural aging. Beyond these surface changes, there is a complex interplay of molecular alterations, encompassing shifts in cellular function, DNA damage, and protein composition disruptions. This data descriptor introduces a unique dataset derived from ten individuals, each with a minimum of 18 years of professional experience as a driver, who are asymmetrically and chronically exposed to solar radiation due to their driving orientation. Skin samples were independently collected from each side of the face using a microdermabrasion-like procedure and analyzed on an Exploris 240 mass spectrometer. Our adapted proteomic statistical framework leverages the sample pairing to provide robust insights. This dataset delves into the molecular differences in exposed skin and serves as a foundational resource for interdisciplinary research in photodermatology, targeted skincare treatments, and computational modelling of skin health.


Assuntos
Face , Espectrometria de Massas , Proteômica , Envelhecimento da Pele , Pele , Pele/efeitos da radiação , Pele/metabolismo , Humanos , Luz Solar
6.
J Am Soc Mass Spectrom ; 35(5): 1055-1058, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38606722

RESUMO

Proximity labeling techniques, such as APEX-MS, provide valuable insights into proximal interactome mapping; however, the verification of biotinylated peptides is not straightforward. With this as motivation, we present a new module integrated into PatternLab for proteomics to enable APEX-MS data interpretation by targeting diagnostic fragment ions associated with APEX modifications. We reanalyzed a previously published APEX-MS data set and report a significant number of biotinylated peptides and, consequently, a confident set of proximal proteins. As the module is part of the widely adopted PatternLab for proteomics software suite, it offers users a comprehensive, easy, and integrated solution for data analysis. Given the broad utility of the APEX-MS technique in various biological contexts, we anticipate that our module will be a valuable asset to researchers, facilitating and enhancing interactome studies. PatternLab's APEX, including a usage protocol, is available at http://patternlabforproteomics.org/apex.


Assuntos
Proteômica , Software , Proteômica/métodos , Espectrometria de Massas/métodos , Humanos , Mapeamento de Interação de Proteínas/métodos , Biotinilação , Peptídeos/análise , Peptídeos/química , Peptídeos/metabolismo
7.
Nutrients ; 16(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38674865

RESUMO

Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD+/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1ß, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.


Assuntos
Fígado Gorduroso Alcoólico , Estresse Oxidativo , Animais , Humanos , Antioxidantes/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado Gorduroso Alcoólico/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Reprod Health ; 20(Suppl 2): 190, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671479

RESUMO

BACKGROUND: Brazil has one of the highest prevalence of cesarean sections in the world. The private health system is responsible for carrying out most of these surgical procedures. A quality improvement project called Adequate Childbirth Project ("Projeto Parto Adequado"- PPA) was developed to identify models of care for labor and childbirth, which place value on vaginal birth and reduce the frequency of cesarean sections without a clinical indication. This research aims to evaluate the implementation of PPA in private hospitals in Brazil. METHOD: Evaluative hospital-based survey, carried out in 2017, in 12 private hospitals, including 4,322 women. We used a Bayesian network strategy to develop a theoretical model for implementation analysis. We estimated and compared the degree of implementation of two major driving components of PPA-"Participation of women" and "Reorganization of care" - among the 12 hospitals and according to type of hospital (belonging to a health insurance company or not). To assess whether the degree of implementation was correlated with the rate of vaginal birth data we used the Bayesian Network and compared the difference between the group "Exposed to the PPA model of care" and the group "Standard of care model". RESULTS: PPA had a low degree of implementation in both components "Reorganization of Care" (0.17 - 0.32) and "Participation of Women" (0.21 - 0.34). The combined implementation score was 0.39-0.64 and was higher in hospitals that belonged to a health insurance company. The vaginal birth rate was higher in hospitals with a higher degree of implementation of PPA. CONCLUSION: The degree of implementation of PPA was low, which reflects the difficulties in changing childbirth care practices. Nevertheless, PPA increased vaginal birth rates in private hospitals with higher implementation scores. PPA is an ongoing quality improvement project and these results demonstrate the need for changes in the involvement of women and the care offered by the provider.


Assuntos
Cesárea , Hospitais Privados , Melhoria de Qualidade , Humanos , Feminino , Cesárea/estatística & dados numéricos , Cesárea/normas , Hospitais Privados/normas , Hospitais Privados/estatística & dados numéricos , Gravidez , Brasil , Adulto , Teorema de Bayes
9.
Biomedicines ; 12(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672246

RESUMO

Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.

10.
Cell Biol Int ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591759

RESUMO

During the morphological changes occurring in osteoblast differentiation, Sonic hedgehog (Shh) plays a crucial role. While some progress has been made in understanding this process, the epigenetic mechanisms governing the expression of Hh signaling members in response to bone morphogenetic protein 7 (BMP7) signaling in osteoblasts remain poorly understood. To delve deeper into this issue, we treated pre-osteoblasts (pObs) with 100 ng/mL of BMP7 for up to 21 days. Initially, we validated the osteogenic phenotype by confirming elevated expression of well-defined gene biomarkers, including Runx2, Osterix, Alkaline Phosphatase (Alp), and bone sialoprotein (Bsp). Simultaneously, Hh signaling-related members Sonic (Shh), Indian (Ihh), and Desert (Dhh) Hedgehog (Hh) exhibited nuanced modulation over the 21 days in vitro period. Subsequently, we evaluated epigenetic markers, and our data revealed a notable change in the CpG methylation profile, considering the methylation/hydroxymethylation ratio. CpG methylation is a reversible process regulated by DNA methyltransferases and demethylases, including Ten-eleven translocation (Tets), which also exhibited changes during the acquisition of the osteogenic phenotype. Specifically, we measured the methylation pattern of Shh-related genes and demonstrated a positive Pearson correlation for GLI Family Zinc Finger 1 (Gli1) and Patched (Ptch1). This data underscores the significance of the epigenetic machinery in modulating the BMP7-induced osteogenic phenotype by influencing the activity of Shh-related genes. In conclusion, this study highlights the positive impact of epigenetic control on the expression of genes related to hedgehog signaling during the morphogenetic changes induced by BMP7 signaling in osteoblasts.

11.
PLoS Negl Trop Dis ; 18(3): e0012072, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38536893

RESUMO

Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.


Assuntos
Injúria Renal Aguda , Fenômenos Biológicos , Bothrops , Mordeduras de Serpentes , Animais , Humanos , Mordeduras de Serpentes/complicações , Bothrops atrox , Proteômica , Injúria Renal Aguda/etiologia
12.
Int J Antimicrob Agents ; 63(5): 107157, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38548248

RESUMO

Cryptococcus neoformans is responsible for over 100 000 deaths annually, and the treatment of this fungal disease is expensive and not consistently effective. Unveiling new therapeutic avenues is crucial. Previous studies have suggested that the anthelmintic drug fenbendazole is an affordable and nontoxic candidate to combat cryptococcosis. However, its mechanism of anticryptococcal activity has been only superficially investigated. In this study, we examined the global cellular response of C. neoformans to fenbendazole using a proteomic approach (data are available via ProteomeXchange with identifier PXD047041). Fenbendazole treatment mostly impacted the abundance of proteins related to metabolic pathways, RNA processing, and intracellular traffic. Protein kinases, in particular, were significantly affected by fenbendazole treatment. Experimental validation of the proteomics data using a collection of C. neoformans mutants led to the identification of critical roles of five protein kinases in fenbendazole's antifungal activity. In fact, mutants lacking the expression of genes encoding Chk1, Tco2, Tco3, Bub1, and Sch9 kinases demonstrated greater resistance to fenbendazole compared to wild-type cells. In combination with the standard antifungal drug amphotericin B, fenbendazole reduced the cryptococcal burden in mice. These findings not only contribute to the elucidation of fenbendazole's mode of action but also support its use in combination therapy with amphotericin B. In conclusion, our data suggest that fenbendazole holds promise for further development as an anticryptococcal agent.


Assuntos
Antifúngicos , Criptococose , Cryptococcus neoformans , Fenbendazol , Proteínas Quinases , Proteômica , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/genética , Antifúngicos/farmacologia , Animais , Fenbendazol/farmacologia , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Camundongos , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Anfotericina B/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Testes de Sensibilidade Microbiana , Modelos Animais de Doenças , Farmacorresistência Fúngica/genética
13.
Infect Immun ; 92(4): e0003724, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38470135

RESUMO

Small molecules are components of fungal extracellular vesicles (EVs), but their biological roles are only superficially known. NOP16 is a eukaryotic gene that is required for the activity of benzimidazoles against Cryptococcus deuterogattii. In this study, during the phenotypic characterization of C. deuterogattii mutants expected to lack NOP16 expression, we observed a reduced EV production. Whole-genome sequencing, RNA-Seq, and cellular proteomics revealed that, contrary to our initial findings, these mutants expressed Nop16 but exhibited altered expression of 14 genes potentially involved in sugar transport. Based on this observation, we designated these mutant strains as Past1 and Past2, representing potentially altered sugar transport. Analysis of the small molecule composition of EVs produced by wild-type cells and the Past1 and Past2 mutant strains revealed not only a reduced number of EVs but also an altered small molecule composition. In a Galleria mellonella model of infection, the Past1 and Past2 mutant strains were hypovirulent. The hypovirulent phenotype was reverted when EVs produced by wild-type cells, but not mutant EVs, were co-injected with the mutant cells in G. mellonella. These results connect EV biogenesis, cargo, and cryptococcal virulence.

14.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474019

RESUMO

Alzheimer's Disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracerebroventricular (ICV) injection of low to moderate doses of streptozotocin (STZ) in adult male Wistar rats can reproduce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, knowledge regarding the molecular aspects of the ICV-STZ model is still incipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on mass spectrometry (MS). To achieve that, samples from the pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differential protein abundance, pathway, and network analysis were performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in the early stages of late-onset Alzheimer's disease (LOAD), based on differentially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further investigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.


Assuntos
Doença de Alzheimer , Ratos , Masculino , Animais , Doença de Alzheimer/metabolismo , Ratos Wistar , Estreptozocina , Proteoma , Proteômica , Modelos Animais de Doenças , Aprendizagem em Labirinto
15.
Anticancer Agents Med Chem ; 24(10): 798-811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500290

RESUMO

INTRODUCTION: Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. METHOD: Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. RESULTS: Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. CONCLUSION: Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.


Assuntos
Antineoplásicos , Venenos de Abelha , Caenorhabditis elegans , Animais , Humanos , Venenos de Abelha/farmacologia , Venenos de Abelha/química , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Estrutura-Atividade , Feminino , Estrutura Molecular
16.
Cell Biol Int ; 48(5): 665-681, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38420868

RESUMO

Epigenetic changes, particularly histone compaction modifications, have emerged as critical regulators in the epigenetic pathway driving endothelial cell phenotype under constant exposure to laminar forces induced by blood flow. However, the underlying epigenetic mechanisms governing endothelial cell behavior in this context remain poorly understood. To address this knowledge gap, we conducted in vitro experiments using human umbilical vein endothelial cells subjected to various tensional forces simulating pathophysiological blood flow shear stress conditions, ranging from normotensive to hypertensive forces. Our study uncovers a noteworthy observation wherein endothelial cells exposed to high shear stress demonstrate a decrease in the epigenetic marks H3K4ac and H3K27ac, accompanied by significant alterations in the levels of HDAC (histone deacetylase) proteins. Moreover, we demonstrate a negative regulatory effect of increased shear stress on HOXA13 gene expression and a concomitant increase in the expression of the long noncoding RNA, HOTTIP, suggesting a direct association with the suppression of HOXA13. Collectively, these findings represent the first evidence of the role of histone-related epigenetic modifications in modulating chromatin compaction during mechanosignaling of endothelial cells in response to elevated shear stress forces. Additionally, our results highlight the importance of understanding the physiological role of HOXA13 in vascular biology and hypertensive patients, emphasizing the potential for developing small molecules to modulate its activity. These findings warrant further preclinical investigations and open new avenues for therapeutic interventions targeting epigenetic mechanisms in hypertensive conditions.


Assuntos
Epigênese Genética , Histonas , Humanos , Histonas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hemodinâmica , Estresse Mecânico , Células Cultivadas
17.
Cad Saude Publica ; 40(2): e00027423, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38381868

RESUMO

Post-COVID-19 syndrome involves a variety of symptoms that last more than 12 weeks after COVID diagnosis. This study aimed to analyze post-COVID-19 syndrome among hospitalized COVID-19 patients 6 and 12 months after hospital discharge. This is an ambidirectional cohort study conducted with individuals who were discharged from three main hospitals in the capital of Mato Grosso State, Brazil, between October and December 2021 and January and March 2022. After data collection from medical records, the individuals were interviewed by telephone 6 and 12 months after hospital discharge, when they were asked about the presence of ongoing or new symptoms and when symptom frequency was evaluated according to sociodemographic and economic characteristics hospitalization, and health conditions. Of all 277 medical records evaluated, 259 patients were eligible to participate in the study, 190 patients six months after discharge and 160 patients 12 months after hospital discharge. At six months, 59% were female patients, 40% were aged 60 years or older, and 87.4% reported at least one symptom. At 12 months, 58.7% were female patients, 37.5% were aged 30 to 49 years, and 67.5% reported at least one symptom. Fatigue was the most common symptom 6 and 12 months after hospital discharge (55.3% and 40.6%, respectively), followed by memory problems (36.8%; 20%), and hair loss (26.8%; 11.2%). The prevalence of post-COVID-19 syndrome was higher among patients of older age, lower income, with hypertension, diabetes, and more severe infection during hospitalization. The risk factors for post-COVID-19 syndrome help understand the long-term effects and the importance of monitoring after the acute phase of the disease.


A síndrome pós-COVID-19 é um termo usado para descrever um conjunto diversificado de sintomas que persistem por mais de 12 semanas da infecção diagnosticada. O objetivo deste estudo foi analisar a síndrome pós-COVID-19 entre hospitalizados por COVID-19 após 6 e 12 meses da alta hospitalar. Trata-se de estudo de coorte ambidirecional, realizado com indivíduos que receberam alta em três dos principais hospitais da capital de Mato Grosso, Brasil, entre outubro e dezembro de 2021 e janeiro e março de 2022. Após coleta de dados em prontuários, os indivíduos foram entrevistados por telefone após 6 e 12 meses da alta hospitalar, sendo questionados sobre a presença de sintomas persistentes ou novos, para a avaliação de sua frequência segundo características sociodemográficas, econômicas, relativas à internação e condições de saúde. Dos 277 prontuários avaliados, 259 pacientes foram elegíveis para o estudo, 190 aos seis meses e 160 após 12 meses da alta hospitalar. Aos seis meses, 59% eram mulheres, 40% com 60 anos ou mais de idade e 87,4% referiram a presença de pelo menos um sintoma. Aos 12 meses, 58,7% eram mulheres, 37,5% com 30 a 49 anos e 67,5% referiram a presença de pelo menos um sintoma. A fadiga foi o sintoma mais comum após 6 e 12 meses de alta hospitalar (55,3% e 40,6%, respectivamente), seguido de problemas de memória (36,8%; 20%) e perda de cabelo (26,8%; 11,2%). Foi maior a prevalência de síndrome pós-COVID-19 entre indivíduos de maior faixa etária, menor renda, hipertensos, diabéticos e com maior gravidade durante a internação. Os fatores de risco da síndrome pós-COVID-19 contribuem para a compreensão dos efeitos a longo prazo e da importância do acompanhamento após a fase aguda da doença.


El síndrome post-COVID-19 es un término utilizado para describir un conjunto diversificado de síntomas que persisten durante más de 12 semanas de la infección diagnosticada. El objetivo fue analizar el síndrome post-COVID-19 entre hospitalizados por COVID-19 tras 6 y 12 meses del alta hospitalaria. Se trata de un estudio de cohorte ambidireccional, realizado con individuos que fueron dados de alta en tres de los principales hospitales de la capital de Mato Grosso, Brasil, entre octubre y diciembre de 2021 y enero y marzo de 2022. Tras recolectar los datos en registros médicos, se entrevistaron los individuos por teléfono tras 6 y 12 meses del alta hospitalaria, cuestionándoles sobre la presencia de síntomas persistentes o nuevos y evaluando su frecuencia conforme las características sociodemográficas, económicas, relacionadas con la hospitalización y condiciones de salud. De los 277 registros médicos evaluados, se eligieron 259 pacientes para el estudio, 190 a los 6 meses y 160 tras 12 meses del alta hospitalaria. A los 6 meses, el 59% eran mujeres, el 40% tenían 60 años o más y el 87,4% refirieron la presencia de al menos un síntoma. A los 12 meses, el 58,7% eran mujeres, el 37,5% tenían entre 30 y 49 años y el 67,5% refirieron la presencia de al menos un síntoma. La fatiga fue el síntoma más común tras 6 y 12 meses del alta hospitalaria (el 55,3% y el 40,6%, respectivamente), seguido de los problemas de memoria (el 36,8% y el 20%) y caída del pelo (el 26,8% y el 11,2%). La prevalencia de síndrome post-COVID-19 fue más alta entre los individuos de mayor edad, menor renta, hipertensos, diabéticos y con mayor gravedad durante la hospitalización. Los factores de riesgo del síndrome post-COVID-19 contribuyen para la comprensión de los efectos a largo plazo y de la importancia del seguimiento tras la fase aguda de la enfermedad.


Assuntos
COVID-19 , Alta do Paciente , Humanos , Feminino , Masculino , Estudos de Coortes , Síndrome de COVID-19 Pós-Aguda , Brasil/epidemiologia , COVID-19/epidemiologia , Hospitalização , Hospitais
18.
Int J Environ Health Res ; : 1-12, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329041

RESUMO

This study aimed to evaluate the practice of physical activity (PA) among adolescents and its association with characteristics of the urban environment of Brazilian capitals. Study with adolescents from the 26 Brazilian capitals and the Federal District participating in the National School Health Survey, 2015 edition. The association between regular practice of PA (≥300 minutes/week) and the dimensions of urban well-being (urban mobility, urban environmental conditions, urban housing conditions, urban collective services, and urban infrastructure) was examined using multilevel logistic regression. A total of 50,904 adolescents were evaluated, among which 20.7% were active. It was observed in the multiple model that adolescents who live in capitals with better urban environmental conditions, such as the presence of tree coverage, less open sewage, and less accumulated garbage around the houses, are more likely to be active (OR = 1.06; 95% CI:1.01;1.12). Adolescents who live in cities with less urban disorder are more likely to be active.

19.
Curr Oncol ; 31(2): 1102-1112, 2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38392076

RESUMO

This study aims to compare whether the use of a salivary substitute including an enzymatic system clinically reduces the intensity of xerostomia, as well as exploring the impact that this has on the quality of life, in patients who had received radiotherapy in the head and neck (HNC) region. Forty patients who had completed radiotherapy treatment within 6 months to 1 year previously were allocated into an Enzymatic Spray group (n = 21) or a Placebo arm (n = 19). It should be noted that two patients in the Placebo arm declined to participate during phase 2 of the study. All patients were randomized and used both products three times a day for 30 days. For analysis, xerostomia grade, unstimulated (UWS) and stimulated (SWS) salivary flow rate, and quality of life through the University of Washington Quality of Life Questionnaire validated in Portuguese (UW-QoL) were assessed in two phases: Phase 1 (before the use of the products) and Phase 2 (after 30 days of using the products). All clinical data were collected from medical records. Analyzing the salivary substitute with the enzymatic system, an improvement in xerostomia complaints was observed 30 days after using the product; however, this difference was not statistically significant (p > 0.05). Regarding quality of life, no significant differences were observed in relation to the UW-QoL and saliva domain between the groups in the two phases of the study (p > 0.05). The salivary substitute with the enzymatic system may be effective in reducing radio-induced xerostomia symptoms; however, further research is necessary to evaluate the efficacy of this salivary substitute on oral health.


Assuntos
Neoplasias de Cabeça e Pescoço , Xerostomia , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Qualidade de Vida , Saliva , Inquéritos e Questionários , Xerostomia/etiologia , Xerostomia/terapia
20.
Epidemiol Serv Saude ; 33: e2023398, 2024.
Artigo em Inglês, Português | MEDLINE | ID: mdl-38265335

RESUMO

OBJECTIVE: To analyze the temporal trend and the spatial distribution of acquired syphilis in Mato Grosso, Brazil, between 2010 and 2021. METHODS: This was an ecological study using notifications of acquired syphilis held on the Notifiable Health Conditions Information System. Detection rates were calculated by health macro-region and three-year periods (2010-2012, 2013-2015, 2016-2018, 2019-2021). The jointpoint method was used to calculate annual percentage change (APC). Thematic maps of Bayesian rates were built and distribution was analyzed using Local Moran. RESULTS: The detection rate increased from 16.2 per 100,000 inhabitants in the first three-year period (2010-2012) to 70.0 in the last three-year period (2019-2021). The Central-North macro-region had the highest rate in the last three years (94.3/100,000 inhab.), while the highest upward trend occurred in the Central-Northwest macro-region, from 2013 to 2018 (APC = 50.2; 95%CI 26.3;78.6). There was an increase in Bayesian rates in most municipalities. CONCLUSION: There was a trend towards an increase in acquired syphilis, especially in the last two three-year periods.


Assuntos
Sífilis , Humanos , Teorema de Bayes , Brasil , Infecções Sexualmente Transmissíveis , Mapeamento Geográfico , Análise Espaço-Temporal
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